This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our lab has recently identified Sox9 as a factor that exclusively marks the stem/progenitor cell compartment in the embryonic pancreas. In this proposal, I will test how Sox9 alters the properties of a cell to ensure that the cell maintains progenitor cell characteristics. By comparing normal progenitors to Sox9-deficient progenitors, I have already determined which genes are activated by Sox9 in the cell. I found that many of these genes are important for allowing cells to make specific connections with other cells, thus ensuring communication between cells. Using time-specific gene inactivation in mice, I here propose to test how inactivation of Sox9 in multipotential pancreas progenitors affects the ability of progenitors to give rise to beta-cells. I will then test whether Sox9 controls beta-cell formation by allowing cells to make appropriate contacts with their neighbors.